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  • 1
    In: Metabolites, MDPI AG, Vol. 13, No. 3 ( 2023-02-24), p. 338-
    Abstract: Direct measurements of temperature-dependent weight gains are experimentally challenging and time-consuming in long-lived/slow-growing organisms such as Antarctic fish. Here, we reassess methodology to quantify the in vivo protein synthesis rate from amino acids, as a key component of growth. We tested whether it is possible to avoid hazardous radioactive materials and whether the analytical pathway chosen is robust against analytical errors. In the eelpout, Pachycara brachycephalum, 13C9H1115N1O2 phenylalanine was injected intraperitoneally and muscle tissue was sampled before injection and at 1.5 h time intervals up to 6 h thereafter. The incorporation of 13C15N-labeled-phenylalanine into muscle was monitored by quantification of bound and free phenylalanine through liquid chromatography–mass spectrometry. We found an increase in the pool of labeled, free phenylalanine in the cytosolic fraction that leveled off after 4.5 h. The labeled phenylalanine bound in the proteins increased linearly over time. The resulting protein synthesis rate (Ks) for P. brachycephalum was as low as 0.049 ± 0.021% day−1. This value and its variability were in good agreement with literature data obtained from studies using radioactive labels, indicating that this methodology is well suited for characterizing growth in polar fish under in situ conditions in remote areas or on research vessels.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662251-8
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  • 2
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 12 ( 2023-06-07), p. 3896-
    Abstract: Plantar plate positioning has been demonstrated as biomechanically superior. However, some operators remain resentful about the morbidity of the surgical approach. To provide improved plate fixation for first tarsometatarsal joint arthrodesis with respect to the tibialis anterior tendon, a medio-plantar plate was developed. The purpose of this biomechanical study was to compare its construct stability to that of a plantar plate construct. Twelve pairs of fresh frozen human specimens were used in a matched pair test. Each pair was fixed with a 4 mm compression screw and either a plantar locking plate or a medio-plantar locking plate. A cantilever beam test was performed in dorsiflexion. Before and after cyclic loading (5000 cycles; 40 N), bending stiffness and relative movements at the joint space were monitored in a quasi-static test including optical motion tracking. Maximum load and bending moment to failure were investigated in a load-to-failure ramp test. The bending stiffness of both groups did not significantly differ before (plantar 49.9 N/mm ± 19.2; medio-plantar 53.9 N/mm ± 25.4, p = 0.43) or after (plantar 24.4 N/mm ± 9.7; medio-plantar 35.3 N/mm ± 22.0, p = 0.08) cyclic loading but decreased significantly in both groups (p 〈 0.01) after cyclic loading. Relative movement increased significantly during cyclic testing in both groups (p 〈 0.01) but did not differ significantly between the groups before (p = 0.29) or after (p = 0.16) cyclic loading. Neither load nor bending moment to failure were significantly different (plantar 225 N ± 78, 10.8 Nm; medio-plantar 210 N ± 86, 10.1 Nm, p = 0.61). Both plate constructs provided equivalent construct stability, both being well suited for Lapidus arthrodesis.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 3
    Online Resource
    Online Resource
    MDPI AG ; 2020
    In:  Atmosphere Vol. 11, No. 4 ( 2020-04-07), p. 355-
    In: Atmosphere, MDPI AG, Vol. 11, No. 4 ( 2020-04-07), p. 355-
    Abstract: NOx emissions from vehicles have been a substantial cause for concern due to their impact on urban air quality. In particular, despite reducing levels of permitted emissions legislatively, such reductions have not been observed in the real world. In this work, NOx emissions from three vehicles—a Euro 5 car, a Euro V hybrid bus, and a Euro VI—bus have been measured in real driving conditions (and in the case of the buses—in full passenger service). A recently developed high spatio-temporal resolution technique combining very fast (10 ms) NOx measurement with differential GPS accurate to 1 cm allows these emissions to be resolved to a distance of less than 10 cm (worst-case—dependent on vehicle speed). The results show that acceleration events for the vehicles play a significant part in their total NOx emissions. In addition, standard events such as a speed bump and a bus stop are analysed. The temperature of any aftertreatment (catalytic converter) to reduce NOx emissions is also observed to be of substantial significance. At idle, the passenger car was observed to near-double its NOx emissions when the air conditioning was switched on. Finally, the real driving conditions are compared to the legislative compliance cycles for the certification of the buses, and those results used to further understand the observed NOx emissions.
    Type of Medium: Online Resource
    ISSN: 2073-4433
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2605928-9
    SSG: 23
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  • 4
    In: Cancers, MDPI AG, Vol. 13, No. 3 ( 2021-01-27), p. 493-
    Abstract: More than 50% of all gynecologic tumors can be classified as rare (defined as an incidence of ≤6 per 100,000 women) and usually have a poor prognosis owing to delayed diagnosis and treatment. In contrast to almost all other common solid tumors, the treatment of rare gynecologic tumors (RGT) is often based on expert opinion, retrospective studies, or extrapolation from other tumor sites with similar histology, leading to difficulty in developing guidelines for clinical practice. Currently, gynecologic cancer research, due to distinct scientific and technological challenges, is lagging behind. Moreover, the overall efforts for addressing these challenges are fragmented across different European countries and indeed, worldwide. The GYNOCARE, COST Action CA18117 (European Network for Gynecological Rare Cancer Research) programme aims to address these challenges through the creation of a unique network between key stakeholders covering distinct domains from concept to cure: basic research on RGT, biobanking, bridging with industry, and setting up the legal and regulatory requirements for international innovative clinical trials. On this basis, members of this COST Action, (Working Group 1, “Basic and Translational Research on Rare Gynecological Cancer”) have decided to focus their future efforts on the development of new approaches to improve the diagnosis and treatment of RGT. Here, we provide a brief overview of the current state-of-the-art and describe the goals of this COST Action and its future challenges with the aim to stimulate discussion and promote synergy across scientists engaged in the fight against this rare cancer worldwide.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 5
    In: Cells, MDPI AG, Vol. 9, No. 6 ( 2020-06-19), p. 1496-
    Abstract: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive malignancy that occurs in young women, is characterized by recurrent loss-of-function mutations in the SMARCA4 gene, and for which effective treatments options are lacking. The aim of this study was to broaden the knowledge on this rare malignancy by reporting a comprehensive molecular analysis of an independent cohort of SCCOHT cases. We conducted Whole Exome Sequencing in six SCCOHT, and RNA-sequencing and array comparative genomic hybridization in eight SCCOHT. Additional immunohistochemical, Sanger sequencing and functional data are also provided. SCCOHTs showed remarkable genomic stability, with diploid profiles and low mutation load (mean, 5.43 mutations/Mb), including in the three chemotherapy-exposed tumors. All but one SCCOHT cases exhibited 19p13.2-3 copy-neutral LOH. SMARCA4 deleterious mutations were recurrent and accompanied by loss of expression of the SMARCA2 paralog. Variants in a few other genes located in 19p13.2-3 (e.g., PLK5) were detected. Putative therapeutic targets, including MAGEA4, AURKB and CLDN6, were found to be overexpressed in SCCOHT by RNA-seq as compared to benign ovarian tissue. Lastly, we provide additional evidence for sensitivity of SCCOHT to HDAC, DNMT and EZH2 inhibitors. Despite their aggressive clinical course, SCCOHT show remarkable inter-tumor homogeneity and display genomic stability, low mutation burden and few somatic copy number alterations. These findings and preliminary functional data support further exploration of epigenetic therapies in this lethal disease.
    Type of Medium: Online Resource
    ISSN: 2073-4409
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2661518-6
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  • 6
    In: Journal of Clinical Medicine, MDPI AG, Vol. 9, No. 6 ( 2020-06-24), p. 1973-
    Abstract: Background: Prostate cancer (PCa) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of prostate adenocarcinomas (n = 492) was utilized. The immune microenvironment was characterized using the CIBERSORTX tool to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Analyses of progression-free survival (PFS), distant metastases, and overall survival (OS) were performed using Kaplan–Meier estimates and Cox regression multivariable analyses. Results: Four immune clusters were identified, largely defined by plasma cell, CD4+ Memory Resting T Cells (CD4 MR), and M0 and M2 macrophage content (CD4 MRHighPlasma CellHighM0LowM2Mid, CD4 MRLowPlasma CellHighM0LowM2Low, CD4 MRHighPlasma CellLowM0HighM2Low, and CD4 MRHighPlasma CellLowM0LowM2High). The two macrophage-enriched/plasma cell non-enriched clusters (3 and 4) demonstrated worse PFS (HR 2.24, 95% CI 1.46–3.45, p = 0.0002) than the clusters 1 and 2. No metastatic events occurred in the plasma cell enriched, non-macrophage-enriched clusters. Comparing clusters 3 vs. 4, in patients treated by surgery alone, cluster 3 had zero progression events (p 〈 0.0001). However, cluster 3 patients had worse outcomes after post-operative radiotherapy (p = 0.018). Conclusion: Distinct tumor immune clusters with a macrophage-enriched, plasma cell non-enriched phenotype and reduced plasma cell enrichment independently characterize an aggressive phenotype in localized prostate cancer that may differentially respond to treatment.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2662592-1
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